This project to investigate the expression of proto-oncogenes and other cell cycle regulatory genes in the embryonic chicken lens seeks to determine their relationship to cell growth, quiescence, and differentiation. The normal developmental profiles of five nuclear proto-oncogene mRNAs (c-myc, N-myc, c-fos, c-jun, and p53) and the cell cycle regulatory protein, cyclin B, have been completed, and the profile of retinoblastoma (Rb) expression is in progress. The finding that cyclin B is present in lens-fiber cells suggests that lens-fiber cell differentiation may represent an aberrant form of the cell cycle. In addition to cyclin B, a number of other proteins normally associated with proliferating cells are expressed in postmitotic, differentiating lens cells. These include cyclin A, c-myc, c-fos, c-jun, and p53. Moreover, preliminary studies using explanted embryonic chicken lens epithelia indicate that the order of expression of these genes during differentiation is the same as during proliferation, a further strengthening the link between differentiation and the cell cycle. The functional role of each of these genes during lens differentiation now is being explored through the use of retroviral vectors, transfection of exogenous DNA, and the production of transgenic mice. In addition, regulatory mechanisms governing the changes in proto-oncogene expression that accompany differentiation are being explored.